Alcohol, Adipose Tissue and Lipid Dysregulation
The first sentence of the abstract reads:
Chronic alcohol consumption perturbs lipid metabolism as it increases adipose tissue lipolysis and leads to ectopic fat deposition within the liver and the development of alcoholic fatty liver disease.
I don’t believe that lipolysis (the breakdown of triglycerides into three fatty acids + glycerol) can be achieved if the insulin level is too high, since excessive serum insulin blocks the action of hormone-sensitive lipase, which is essential to lipolysis (think of a bear eating berries in preparation for hibernation: lipolysis is not desirable, when storing fat is the order of the day). All that is required for fat deposition in the liver is exceeding the capacity of the metabolic pathway that handles ethanol/fructose/branched-chain amino acids.
My primary interest is to determine the effects of consuming ethanol on ketosis and fat metabolism generally. There is some very interesting stuff in the OP linked paper. For example:
Additionally, feeding 5 g/kg/day of alcohol along with a high fat diet (59% fat) prevented the high fat diet induced increase in eWAT mass, suggesting that dietary fat composition has the potential to modulate the alcoholic effect [25].
That trailing link (25) goes here:
As does saturated fat consumption, which supposedly protects the liver. (As does berberine.)
I originally linked the following in another thread. But I think it warrants more attention, so I’ve linked it here as well.
There is lots of very interesting stuff here. For example:
Discussion
… ethanol is more ketogenic that iso-caloric fat.
… The key role played by alcohol is confirmed by our finding that a diet consisting of alcohol (46% of calories) and fat (36% of calories) is far more ketogenic than a high fat diet alone (82% of total calories), though both had the same low carbohydrate content.
… the alcohol effect upon ketogenesis was predominant in the fasting state, when alcohol had disappeared from the blood and when its metabolic effects upon the redox potential of the cells had already regressed…
There are additionally 41 citations included.
PS: Hopefully, I don’t really have to say this, but I will anyway to avoid any confusion. I am not advocating a keto diet consisting of 46% ethanol. Could we call that the EKD? What I’m saying is that apparently, and I stand to be corrected if I’ve misunderstood, drinking alcoholic beverages in moderation while in ketosis and eating lots of fat may help maintain higher ketone levels than not doing so. Moderation is the key here and it’s likely different for everyone. Too much and the resulting damage is well documented. A little goes a long way, I suppose. Cheers!
Slipping up on Keto
Wow. This is fascinating. Thanks.
I need to think about this some… and how it links with some recent experiments ive made with a CGM -
To my surprise, drinking wine (which I avoided on keto for years simce I assumed it was just carbs) brought my glucose down drastically, every time.
What I was thinking when I first saw that was that alcohol interfered with gluconeogenesis somehow.
I wondered though… whether this applies to low carbers in which I assume GNG is pronounced, or to just anyone regardless of diet.
I can find reasoning for both claims.
But, if I understand what they say in this paper correctly -
"Thus, the hyperketonemia and ketonuria observed after alcohol consumption cannot be attributed to an immediate effect of alcohol, but is the consequence of a delayed change in intermediary metabolism characterized by increased hepatic ketone production from fatty acids, possibly linked to ethanol-induced glycogen depletion and depression of citric acid cycle activity." -
This supports my hunch that ethanol suppresses GNG by depressing the citric acid cycle…
Also, keep in mind that ethanol, whatever its other attributes, contains 7 cals energy per gram. That’s a lot of energy that does not have to come from glucose - plus it can not be stored in any form. Any excess just gets pissed out. It’s also very easily utilized energy, and I suspect that’s why one’s metabolism uses it first when available. I don’t buy the ‘it’s toxic and your body wants to get rid of it ASAP’ argument. If ethanol fills the need for immediate energy, I can see GNC ramping down while it does so. That might also explain why/how it gets to the brain so quickly.
Not sure that I understand, but alcohol may contribute to lower blood glucose? Here’s a story.
I have recently (3 months ago) abstained from alcohol entirely. It appears that my average blood sugar has risen. I was almost completely carnivore diet also. As a T2D, my A1C was in the pre-diabetic range at my last test a year ago (without any medication). At that time, I was drinking moderate amounts of dry white wine with my keto diet. Now without the alcohol, I am surprised that my blood sugar has crept up.
I believe my liver is producing glucose via gluconeogenis, so I have began Metformin once again to reduce the gluconeogenisis…it is working. But perhaps, the moderate alcohol consumption is just as effective?
Thoughts?
This is probably the result of an insulin response to the carbohydrate in the wine. You should get less of a response from hard liquor, which contains less or no carbohydrate.
Ethanol, fructose, and branched-chain amino acids are all dealt with by the same metabolic pathway in the liver, which has a limited capacity and is fairly easily overwhelmed. Hence the propensity to fatty liver disease when we overindulge in liquor and/or sugar.
But this pathway, as I understand things, is separate from the pathway that generates glucose (usually out of amino acids). Gluconeogenesis is stimulated by glucagon and inhibited by insulin, so a diet low in carbohydrate which raises glucagon relative to insulin, thereby stimulates gluconeogenesis, whereas a diet high in carbohydrate releases enough glucose into the bloodstream to inhibit glucagon and stimulate insulin, which in turn inhibits gluconeogenesis and ketogenesis. (There are other factors that limit gluconeogenesis, as well, to keep it commensurate with demand.)
There’s also this possibility. Cheaper and less potential undesirable downside effects:
Big Blood Sugar Swings
I highly doubt this. What you’re implying is that a decrease in blood sugar is caused by eating carbs. It’s not going to happen. At least not for normal people. (There’s always an exception.) In all the time I wore a CGM, I never saw a decrease in blood sugar by eating carbs.
And if it did work this way, then those of us who eat lean meats should get a decrease in blood sugar, as I’m sure we get very high insulin levels, if one is eating 150+ grams of protein in one meal. I never saw a decrease in blood sugar, no matter how much protein I ate. (NOTE: this is not true for all. Jimmy Moore tried a PSMF and got hypoglycemia.)
I also note that I tested ACV, 1 tablespoon in water and never saw a decrease in blood sugar while wearing my CGM. Tested a few times.
I was never able to verify a decrease in blood sugar caused by alcohol, either, as I only drank at night…when my blood sugar was going down anyway.
My apologies. My earlier comment assumed that the blood-sugar-lowering effect of insulin was understood by all. When we eat carbohydrate, there is an initial rise in serum glucose. This hyperglycaemia is a problem for the body, so the pancreas mobilises to secrete insulin to drive the excess glucose into muscle (to be metabolised) and into adipose tissue (to be stored as triglycerides). The result is a dip in serum glucose, typically to a level below what it was before eating. This is the mechanism that causes the sugar/carb crash we all experienced when eating high carbohydrates. The low sometimes reaches to hypoglycaemic levels, hence the advice to those eating a standard American diet to eat three meals a day, with snacks in between and before bedtime.
This dip in serum glucose, by the way, is what people on these forums have used to determine that certain artificial sweeteners have an effect on their insulin levels. Since there is no home insulin test, the pattern of glucose levels is used to infer whether or not there has been an insulin response.
As Bikman’s research has shown, it is actually the ratio of insulin to glucagon that is the relevant datum, not so much their absolute values. In a high-carb diet, protein eaten along with the carbohydrate stimulates an insulin response that is about half the response to an equivalent amount of carbohydrate. Since the quantity of carbohydrate eaten inhibits the secretion of glucagon, this means that the insulin/glucagon ratio rises very high.
In a ketogenic low-carb diet, however, protein stimulates the secretion not only of insulin, but of glucagon, with the result that that the insulin/glucagon ratio changes very little, if at all. In all cases, fat stimulates only the bare minimum of insulin consistent with survival, which is a negligible amount, so the insulin/glucagon ratio remains unaffected.
I think there are some important details missing.
Blood glucose patterns are anything but simple.
Not every carb causes the same wave pattern obviously and it differs wildly between people, food, and timing to mention a few.
What I suggested was that my glucose dipped drastically, i.e without showing any spiking before that.
Im looking for my logs so I can take a look at it again… but cant find them yet 
Another event which I remember clearly was that following a high-carb late-night meal with wine, seemed to have prevented a phenomenon the CGM brought very vividly to my attention where my glucose would spike several times during my sleep instead of being normally lower than my daytime average.
It could have been the wine (which was the only different variable in that occassion) but unfortunately there was a limited amout of beatings I was willing to give myself in the name of science and “know thyself” 
Well said, Michael.
For many people, it is as simple as that - a little booze lowers their blood sugar; even the next morning it’s lower. (No judgment or drawing a balance of net positives and negatives here.)
Usually, the concern with this is for people who are outright fasting. We’re not eating anything, and primarily using our own fat for energy. Most of the body runs fine on ketones, but the tissues that do need glucose really need it, and if we stop the liver from making glucose, then it can be dangerous.
Regardless of diet, there is the aspect of the liver “dropping everything else” and getting to work on the alcohol; it’s ‘all hands on deck,’ there. If - as with fasting for some days or more - our glycogen stores are down, and the whole alimentary canal and digestive system is emptied out, then the cessation of gluconeogenesis by the liver can make for a relatively precipitous drop in blood sugar. “Low carbers,” per se, usually still have a less immediate need for minute-by-minute glucose production from the liver, versus a totally ‘emptied out’ person who’s been fasting for days.
There is no one blood sugar level where trouble starts for people or where they feel ‘bad.’ I’ve seen people say that 70 mg/dl or 3.9 mmol/L made them feel faint and weak, while others do fine down through 50 / 2.8 and 40 / 2.2.
To generalize, I think being well and truly ‘fat-adapted’ helps with tolerance for lower blood sugar - if as much of the body is running on ketones as it can, then less glucose is necessary. Makes sense, no?
Long-fasting individuals have even gotten down around 30 / 1.65 while feeling all right and engaging in their daily activities. I don’t know if they are a minority, but IMO at that level a good many people are not going to be feeling good. For a really extreme example, the Scotsman Angus Barbieri, he of the very long fast, recorded a 17 / 0.95 one time, and this was while he was going about his normal life, walking around the city, etc. Mind-blowing, IMO.
There are several things here. Hyperketonemia - sure, because that’s not dependent on the blood sugar level. Whether or not the liver quits making glucose, as long as enough more ketones show up, then that’s satisfied.
I’m not sure of the time frames here. “A delayed change in intermediary metabolism” sounds like it’s going to take a while, versus the more rapid effects of alcohol on, for example, a fasting person. But perhaps not.
That said, alcohol in the human body can and does depress the citric acid cycle. This is going to happen, regardless of whether the liver making glucose is required or not. I see it going hand-in-hand with the suppression of liver glucose production.
The steps in alcohol metabolism - acetaldehyde/acetate - both change NAD to NADH. NAD is “nicotinamide adenine dinucleotide,” which is involved in a whole bunch of stuff in the body, and NADH is its reduced form. The increased NADH directly inhibits the citric acid cycle (as well as fatty acid oxidation, which contributes to ‘fatty liver’).
From all I can see, this is going to go on, whether or not the liver was producing glucose beforehand.
I think that as long as there is enough glucose to feed the red blood corpuscles and other cells that need it, ketones can pretty much take up the slack.
The brain is supposed to need a certain minimum of glucose, but Benjamin Bikman has publicly challenged that notion; he says it’s not proved that the brain needs any glucose at all. George Cahill came close to showing this, during his experiments on fasting subjects. One day, they applied a euglycaemic hyperinsulinaemic clamp to their subjects, who by that time had elevated ketones from fasting. They were able to drive the subjects’ blood sugar down to levels that would normally cause coma or death, but the subjects were fine, because their abundant ketones were supplying their brains. (This would be considered highly unethical these days, and was dodgy even back then.)
I suspect that, at some point, glucagon would rise high enough to force the liver back into gluconeogenesis, if the process were halted long enough.